Dynamin 2 is essential for mammalian spermatogenesis (#459)

School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW, Australia

PRC in Reproductive Science, University of Newcastle, Callaghan, NSW, Australia

School of Pharmacy and Biomedical Science, University of Newcastle, Callaghan, NSW, Australia

School of Biological Sciences, University of Auckland, Auckland, New Zealand

The dynamin family of proteins have long been known to play important regulatory roles in membrane remodelling and endocytosis, especially within brain and neuronal cell types. In the male reproductive tract, dynamin 1 (DNM1) and dynamin 2 (DNM2) have recently been shown to act as key mediators of sperm acrosome formation and function. However, little is known about the roles that these proteins play in the developing germ cells during spermatogenesis. In this study, we employed the use of a DNM2 germ cell-specific knockout model to investigate the role of DNM2 in spermatogenesis. We demonstrate that ablation of DNM2 in early spermatogenesis results in germ cell arrest during prophase I of meiosis, subsequent loss of all post-meiotic germ cells and concomitant sterility. These effects become exacerbated with age, and ultimately result in the demise of the spermatogonial stem cell population and a Sertoli cell only phenotype. We also demonstrate that this activity may be temporally regulated by phosphorylation of DNM2 via the cyclin dependent kinase 1 (CDK1) in early spermatogonial cells, and dephosphorylation by phosphatase PPP3CA in meiotic and post-meiotic spermatogenesis.